Brain Structure and Function

, 213:343 | Cite as

The extreme capsule in humans and rethinking of the language circuitry

  • Nikos Makris
  • Deepak N. Pandya
Original Article


Experimental and imaging studies in monkeys have outlined various long association fiber pathways within the fronto-temporo-parietal region. In the present study, the trajectory of the extreme capsule (EmC) fibers has been delineated in five human subjects using DT-MRI tractography. The EmC seems to be a long association fiber pathway, which courses between the inferior frontal region and the superior temporal gyrus extending into the inferior parietal lobule. Comparison of EmC fibers with the adjacent association fiber pathway, the middle longitudinal fascicle (MdLF), in the same subjects reveals that EmC is located in a medial and rostral position relative to MdLF flanking in part the medial wall of the insula. The EmC can also be differentiated from other neighboring fiber pathways such as the external capsule, uncinate fascicle, arcuate fascicle, superior longitudinal fascicles II and III, and the inferior longitudinal fascicle. Given the location of EmC within the language zone, specifically Broca’s area in the frontal lobe, and Wernicke’s area in the temporal lobe and inferior parietal lobule, it is suggested that the extreme capsule could have a role in language function.


Diffusion imaging DT-MRI Tractography Language Extreme capsule 



Preparation of this article was supported in part by grants from: the National Institutes of Health National Center for Complementary and Alternative Medicine (NCCAM) to Dr. Nikos Makris. The authors gratefully acknowledge Dr. Edward H. Yeterian, Dr. Larry Seidman, Jonathan Kaiser, Danielle Sliva, George Papadimitriou, Steve Hodge, Thomas Benner and Dr. Andre van der Kouwe for their valuable contributions to the preparation of this manuscript. Offprints: Nikos Makris, M.D., Ph.D., Center for Morphometric Analysis, Massachusetts General Hospital, 149 13th St., Room 6017, Charlestown, MA.


  1. Ariens-Kappers CU, Huber GC, Crosby EC (1936) The comparative anatomy of the nervous system of vertebrates including man. MacMillan, New YorkGoogle Scholar
  2. Azuma M, Suzuki H (1984) Properties and distribution of auditory neurons in the dorsolateral prefrontal cortex of the alert monkey. Brain Res 298(2):343–346. doi: 10.1016/0006-8993(84)91434-3 CrossRefPubMedGoogle Scholar
  3. Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 111:209–219. doi: 10.1006/jmrb.1996.0086 CrossRefPubMedGoogle Scholar
  4. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed 15(7–8):435–455. doi: 10.1002/nbm.782 CrossRefPubMedGoogle Scholar
  5. Benson DA, Hienz RD, Goldstein MH Jr (1981) Single-unit activity in the auditory cortex of monkeys actively localizing sound sources: spatial tuning and behavioral dependency. Brain Res 219(2):249–267. doi: 10.1016/0006-8993(81)90290-0 CrossRefPubMedGoogle Scholar
  6. Berke JJ (1960) The claustrum, the external capsule and the extreme capsule of Macaca mulatto. J Comp Neurol 115(3):297–331. doi: 10.1002/cne.901150304 CrossRefGoogle Scholar
  7. Catani M, Howard RJ, Pajevic S, Jones DK (2002) Virtual in vivo interactive dissection of white matter fasciculi in the human brain. Neuroimage 17(1):77–94. doi: 10.1006/nimg.2002.1136 CrossRefPubMedGoogle Scholar
  8. Catani M, Jones DK, ffytche DH (2005) Perisylvian language networks of the human brain. Ann Neurol 57(1):8–16. doi: 10.1002/ana.20319 CrossRefPubMedGoogle Scholar
  9. Caviness VSJ, Makris N, Meyer J, Kennedy DN (1996) MRI-based parcellation of human neocortex: an anatomically specified method with estimate of reliability. J Cogn Neurosci 8:566–588Google Scholar
  10. Clarke S, Bellmann Thiran A, Maeder P, Adriani M, Vernet O, Regli L, Cuisenaire O, Thiran JP (2002) What and where in human audition: selective deficits following focal hemispheric lesions. Exp Brain Res 147(1):8–15. doi: 10.1007/s00221-002-1203-9 CrossRefPubMedGoogle Scholar
  11. Clarke S, Thiran AB (2004) Auditory neglect: what and where in auditory space. Cortex 40(2):291–300. doi: 10.1016/S0010-9452(08)70124-2 CrossRefPubMedGoogle Scholar
  12. Crosby EC, Schnizlein HN (1982) Comparative correlative neuroanatomy of the vertebrate telencephalon. Macmillan, New YorkGoogle Scholar
  13. Dejerine J (1895) Anatomie des Centres Nerveux. Tome 1. Paris, France, Rueff et CieGoogle Scholar
  14. Dejerine J (1901) Anatomie des Centres Nerveux. Tome 2. Paris, France, Rueff et CieGoogle Scholar
  15. Ding G, Jiang Q, Li L, Zhang L, Zhang ZG, Ledbetter KA, Panda S, Davarani SP, Athiraman H, Li Q, Ewing JR, Chopp M (2008) Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats. J Cereb Blood Flow Metab 28(8):1440–1448. doi: 10.1038/jcbfm.2008.33 CrossRefPubMedGoogle Scholar
  16. Filipek PA, Richelme C, Kennedy DN, Caviness VS Jr (1994) The young adult human brain: an MRI-based morphometric analysis. Cereb Cortex 4:344–360. doi: 10.1093/cercor/4.4.344 CrossRefPubMedGoogle Scholar
  17. Fullerton BC, Pandya DN (2007) Architectonic analysis of the auditory-related areas of the superior temporal region in human brain. J Comp Neurol 504(5):470–498. doi: 10.1002/cne.21432 CrossRefPubMedGoogle Scholar
  18. Frey S, Campbell JS, Pike GB, Petrides M (2008) Dissociating the human language pathways with high angular resolution diffusion fiber tractography. J Neurosci 28(45):11435–11444CrossRefPubMedGoogle Scholar
  19. Geschwind N (1965a) Disconnexion syndromes in animals and man. I. Brain 88(2):237–294. doi: 10.1093/brain/88.2.237 CrossRefPubMedGoogle Scholar
  20. Geschwind N (1965b) Disconnexion syndromes in animals and man. II. Brain 88(3):585–644. doi: 10.1093/brain/88.3.585 CrossRefPubMedGoogle Scholar
  21. Hackett TA, Preuss TM, Kaas JH (2001) Architectonic identification of the core region in auditory cortex of macaques, chimpanzees, and humans. J Comp Neurol 441(3):197–222. doi: 10.1002/cne.1407 CrossRefPubMedGoogle Scholar
  22. Hackett TA, Stepniewska I, Kaas JH (1999) Prefrontal connections of the parabelt auditory cortex in macaque monkeys. Brain Res 817(1–2):45–58. doi: 10.1016/S0006-8993(98)01182-2 CrossRefPubMedGoogle Scholar
  23. Jiang Q, Zhang ZG, Ding GL, Silver B, Zhang L, Meng H, Lu M, Pourabdillah-Nejed DS, Wang L, Savant-Bhonsale S, Li L, Bagher-Ebadian H, Hu J, Arbab AS, Vanguri P, Ewing JR, Ledbetter KA, Chopp M (2006) MRI detects white matter reorganization after neural progenitor cell treatment of stroke. Neuroimage 32(3):1080–1089. doi: 10.1016/j.neuroimage.2006.05.025 CrossRefPubMedGoogle Scholar
  24. Kaas JH, Hackett TA (1999) ‘What’ and ‘where’ processing in auditory cortex. Nat Neurosci 2(12):1045–1047. doi: 10.1038/15967 CrossRefPubMedGoogle Scholar
  25. Kaas JH, Hackett TA (2000) Subdivisions of auditory cortex and processing streams in primates. Proc Natl Acad Sci USA 97(22):11793–11799. doi: 10.1073/pnas.97.22.11793 CrossRefPubMedGoogle Scholar
  26. Klingberg T, Hedehus M, Temple E, Salz T, Gabrieli JD, Moseley ME, Poldrack RA (2000) Microstructure of temporo-parietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging. Neuron 25(2):493–500. doi: 10.1016/S0896-6273(00)80911-3 CrossRefPubMedGoogle Scholar
  27. Krieg WJS (1963) Connections of the cerebral cortex. Brain Books, EvanstonGoogle Scholar
  28. Leinonen L, Hyvarinen J, Sovijarvi AR (1980) Functional properties of neurons in the temporo-parietal association cortex of awake monkey. Exp Brain Res 39(2):203–215. doi: 10.1007/BF00237551 CrossRefPubMedGoogle Scholar
  29. Lori NF, Akbudak E, Shimony JS, Cull TS, Snyder AZ, Guillory RK, Conturo TE (2002) Diffusion tensor fiber tracking of human brain connectivity: acquisition methods, reliability analysis and biological results. NMR Biomed 15(7–8):494–515. doi: 10.1002/nbm.779 CrossRefPubMedGoogle Scholar
  30. Makris N (1999) Delineation of human association fiber pathways using histologic and magnetic resonance methodologies. Behavioral neuroscience. Boston University, Boston, p 176Google Scholar
  31. Makris N, Kennedy DN, McInerney S, Sorensen AG, Wang R, Caviness VS Jr, Pandya DN (2005) Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study. Cereb Cortex 15(6):854–869. doi: 10.1093/cercor/bhh186 CrossRefPubMedGoogle Scholar
  32. Makris N, Pandya DN, Normandin JJ (2002) Quantitative DT-MRI investigations of the human cingulum bundle. Cent Nerv Syst Spectrums 7(7):522–528Google Scholar
  33. Makris N, Papadimitriou GM, Kaiser JR, Sorg S, Kennedy DN, Pandya DN (2008) Delineation of the middle longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study. Cereb Cortex (in press)Google Scholar
  34. Makris N, Papadimitriou GM, Sorg S, Kennedy DN, Caviness VS, Pandya DN (2007) The occipitofrontal fascicle in humans: a quantitative, in vivo, DT-MRI study. Neuroimage 37(4):1100–1111. doi: 10.1016/j.neuroimage.2007.05.042 CrossRefPubMedGoogle Scholar
  35. Makris N, Worth AJ, Sorensen AG, Papadimitriou GM, Wu O, Reese TG, Wedeen VJ, Davis TL, Stakes JW, Caviness VS, Kaplan E, Rosen BR, Pandya DN, Kennedy DN (1997) Morphometry of in vivo human white matter association pathways with diffusion-weighted magnetic resonance imaging. Ann Neurol 42(6):951–962. doi: 10.1002/ana.410420617 CrossRefPubMedGoogle Scholar
  36. Martinkauppi S, Rama P, Aronen HJ, Korvenoja A, Carlson S (2000) Working memory of auditory localization. Cereb Cortex 10(9):889–898. doi: 10.1093/cercor/10.9.889 CrossRefPubMedGoogle Scholar
  37. Mesulam MM (1998) From sensation to cognition. Brain 121(Pt 6):1013–1052. doi: 10.1093/brain/121.6.1013 CrossRefPubMedGoogle Scholar
  38. Mori S, Crain BJ, Chacko VP, van Zijl PC (1999) Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45(2):265–269. doi:10.1002/1531-8249(199902)45:2<265::AID-ANA21>3.0.CO;2-3CrossRefPubMedGoogle Scholar
  39. Morosan P, Rademacher J, Schleicher A, Amunts K, Schormann T, Zilles K (2001) Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system. Neuroimage 13(4):684–701. doi: 10.1006/nimg.2000.0715 CrossRefPubMedGoogle Scholar
  40. Ojemann G, Ojemann J, Lettich E, Berger M (1989) Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. J Neurosurg 71(3):316–326PubMedCrossRefGoogle Scholar
  41. Ojemann JG, McKinstry RC, Mukherjee P, Park TS, Burton H (2005) Hand somatosensory cortex activity following selective dorsal rhizotomy: report of three cases with fMRI. Childs Nerv Syst 21(2):115–121. doi: 10.1007/s00381-004-1051-y CrossRefPubMedGoogle Scholar
  42. Petrides M, Pandya DN (1984) Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J Comp Neurol 228(1):105–116. doi: 10.1002/cne.902280110 CrossRefPubMedGoogle Scholar
  43. Petrides M, Pandya DN (1988) Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey. J Comp Neurol 273(1):52–66. doi: 10.1002/cne.902730106 CrossRefPubMedGoogle Scholar
  44. Petrides M, Pandya DN (2006) Efferent association pathways originating in the caudal prefrontal cortex in the macaque monkey. J Comp Neurol 498(2):227–251. doi: 10.1002/cne.21048 CrossRefPubMedGoogle Scholar
  45. Petrides M, Pandya DN (2007) Efferent association pathways from the rostral prefrontal cortex in the macaque monkey. J Neurosci 27(43):11573–11586. doi: 10.1523/JNEUROSCI.2419-07.2007 CrossRefPubMedGoogle Scholar
  46. Petrides M, Pandya DN (2008) Neural circuitry underlying language. In: Marien P, Abutalebi J (eds) Neuropsychological research: a review. Psychology Press, London, pp 22–60Google Scholar
  47. Pierpaoli C, Barnett A, Pajevic S, Chen R, Penix LR, Virta A, Basser P (2001) Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 13(6 Pt 1):1174–1185CrossRefPubMedGoogle Scholar
  48. Pierpaoli C, Basser PJ (1996) Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 36(6):893–906. doi: 10.1002/mrm.1910360612 CrossRefPubMedGoogle Scholar
  49. Rademacher J, Galaburda AM, Kennedy DN, Filipek PA, VSj Caviness (1992) Human cerebral cortex: localization, parcellation, and morphometry with magnetic resonance imaging. J Cogn Neurosci 4(4):352–374. doi: 10.1162/jocn.1992.4.4.352 CrossRefGoogle Scholar
  50. Rauschecker J (1995) Compensatory plasticity and sensory substitution in the cerebral cortex. Trends Neurosci 18:36–43. doi: 10.1016/0166-2236(95)93948-W CrossRefPubMedGoogle Scholar
  51. Rauschecker JP, Tian B (2000) Mechanisms and streams for processing of “what” and “where” in auditory cortex. Proc Natl Acad Sci USA 97(22):11800–11806. doi: 10.1073/pnas.97.22.11800 CrossRefPubMedGoogle Scholar
  52. Rilling JK, Glasser MF, Preuss TM, Ma X, Zhao T, Hu X, Behrens TE (2008) The evolution of the arcuate fasciculus revealed with comparative DTI. Nat Neurosci 11(4):426–428CrossRefPubMedGoogle Scholar
  53. Romanski LM, Bates JF, Goldman-Rakic PS (1999a) Auditory belt and parabelt projections to the prefrontal cortex in the rhesus monkey. J Comp Neurol 403(2):141–157. doi:10.1002/(SICI)1096-9861(19990111)403:2<141::AID-CNE1>3.0.CO;2-VCrossRefPubMedGoogle Scholar
  54. Romanski LM, Tian B, Fritz J, Mishkin M, Goldman-Rakic PS, Rauschecker JP (1999b) Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex. Nat Neurosci 2(12):1131–1136. doi: 10.1038/16056 CrossRefPubMedGoogle Scholar
  55. Saur D, Kreher BW, Schnell S, Kummerer D, Kellmeyer P, Vry MS, Umarova R, Musso M, Glauche V, Abel S, Huber W, Rijntjes M, Hennig J, Weiller C (2008) Ventral and dorsal pathways for language. Proc Natl Acad Sci USA 105(46):18035–18040CrossRefPubMedGoogle Scholar
  56. Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. Oxford University Press, New YorkGoogle Scholar
  57. Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, Wedeen VJ (2007) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130(Pt 3):630–653. doi: 10.1093/brain/awl359 CrossRefPubMedGoogle Scholar
  58. Seltzer B, Pandya DN (1984) Further observations on parieto-temporal connections in the rhesus monkey. Exp Brain Res 55(2):301–312. doi: 10.1007/BF00237280 CrossRefPubMedGoogle Scholar
  59. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme Medical Publishers, Inc, New YorkGoogle Scholar
  60. Vaadia E, Benson DA, Hienz RD, Goldstein MH Jr (1986) Unit study of monkey frontal cortex: active localization of auditory and of visual stimuli. J Neurophysiol 56(4):934–952PubMedGoogle Scholar
  61. Wernicke C (1874) Der aphasiche Symptomenkomplex. Cohn und Weigert, BreslauGoogle Scholar
  62. Werring DJ, Toosy AT, Clark CA, Parker GJ, Barker GJ, Miller DH, Thompson AJ (2000) Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke. J Neurol Neurosurg Psychiatry 69(2):269–272. doi: 10.1136/jnnp.69.2.269 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Departments of Psychiatry and NeurologyHarvard Medical SchoolBostonUSA
  2. 2.Department of Anatomy and NeurobiologyBoston University School of MedicineBostonUSA
  3. 3.Center for Morphometric Analysis, A. Martinos Center for Biomedical Imaging, Massachusetts General HospitalCharlestownUSA

Personalised recommendations